DOI: 10.1073/pnas.071066598. A role for intermolecular disulfide bonds in prion diseases?

A role for intermolecular disulfide bonds in prion diseases?

10.1073/pnas.071066598

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The key event in prion diseases seems to be the conversion of the prion protein PrP from its normal cellular isoform (PrP C ) to an aberrant “scrapie” isoform (PrP Sc ). Earlier studies have detected no covalent modification in the scrapie isoform and have concluded that the PrP C → PrP Sc conversion is a purely conformational transition involving no chemical reactions. However, a reexamination of the available biochemical data suggests that the PrP C → PrP Sc conversion also involves a covalent reaction of the (sole) intramolecular disulfide bond of PrP C . Specifically, the data are consistent with the hypothesis that infectious prions are composed of PrP Sc polymers linked by intermolecular disulfide bonds. Thus, the PrP C → PrP Sc conversion may involve not only a conformational transition but also a thiol/disulfide exchange reaction between the terminal thiolate of such a PrP Sc polymer and the disulfide bond of a PrP C monomer. This hypothesis seems to account for several unusual features of prion diseases.

Bibliography

Welker, E., Wedemeyer, W. J., & Scheraga, H. A. (2001). A role for intermolecular disulfide bonds in prion diseases? Proceedings of the National Academy of Sciences, 98(8), 4334â4336.

Authors 3

Ervin Welker (first)
William J. Wedemeyer (additional)
Harold A. Scheraga (additional)

References 35 Referenced 54

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:23 p.m.)
Indexed	2 weeks, 2 days ago (Aug. 12, 2025, 5:34 p.m.)
Issued	24 years, 5 months ago (March 27, 2001)
Published	24 years, 5 months ago (March 27, 2001)
Published Online	24 years, 5 months ago (March 27, 2001)
Published Print	24 years, 4 months ago (April 10, 2001)

Funders 0

None

BibTeX

@article{Welker_2001, title={A role for intermolecular disulfide bonds in prion diseases?}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.071066598}, DOI={10.1073/pnas.071066598}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Welker, Ervin and Wedemeyer, William J. and Scheraga, Harold A.}, year={2001}, month=mar, pages={4334–4336} }

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  "abstract": "<jats:p>\n            The key event in prion diseases seems to be the conversion of the\n prion protein PrP from its normal cellular isoform (PrP\n            <jats:sup>C</jats:sup>\n            )\n to an aberrant \u201cscrapie\u201d isoform (PrP\n            <jats:sup>Sc</jats:sup>\n            ). Earlier\n studies have detected no covalent modification in the scrapie isoform\n and have concluded that the PrP\n            <jats:sup>C</jats:sup>\n            \u2192 PrP\n            <jats:sup>Sc</jats:sup>\n            conversion is a purely conformational transition involving no chemical\n reactions. However, a reexamination of the available biochemical data\n suggests that the PrP\n            <jats:sup>C</jats:sup>\n            \u2192 PrP\n            <jats:sup>Sc</jats:sup>\n            conversion\n also involves a covalent reaction of the (sole) intramolecular\n disulfide bond of PrP\n            <jats:sup>C</jats:sup>\n            . Specifically, the data are\n consistent with the hypothesis that infectious prions are composed of\n PrP\n            <jats:sup>Sc</jats:sup>\n            polymers linked by intermolecular disulfide bonds.\n Thus, the PrP\n            <jats:sup>C</jats:sup>\n            \u2192 PrP\n            <jats:sup>Sc</jats:sup>\n            conversion may\n involve not only a conformational transition but also a\n thiol/disulfide exchange reaction between the terminal thiolate of\n such a PrP\n            <jats:sup>Sc</jats:sup>\n            polymer and the disulfide bond of a\n PrP\n            <jats:sup>C</jats:sup>\n            monomer. This hypothesis seems to account for several\n unusual features of prion diseases.\n          </jats:p>",
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